The invention concerns a process for the preparation of 3-chlorophthalide by the hydrolysis of o-pentachloroxylene with water.
3-Chlorophthalide, which is also known as 3-chloro[3H]-isobenzofuranone-1, or as the pseudochloride of phthalaldehydic acid, and is abbreviated hereinbelow as 3-CP, serves in addition to 3-bromophthalide as an intermediate for the introduction of the phthalidyl moiety in organic syntheses.
3-Chlorophthalide is prepared by classical methods either by the chlorination of phthalide or from phthalaldehydic acid and thionyl chloride (Gabriel, Berichte 49, [1916] 1612): ##STR1##
Both processes, however, set out from compounds which themselves must be prepared by a multiple-step synthesis.
3-Chlorophthalide, however, can also by prepared by hydrolysis of pentachloro-o-xylene (.alpha.,.alpha.,.alpha.,.alpha.',.alpha.'-pentachloro-o-xylene or o-dichloromethyltrichloromethylbenzene), abbreviated hereinbelow as o-PCX, which is easily obtainable by the chlorination of o-xylene. ##STR2##
It is known, however, that this hydrolysis of o-PCX is difficult and does not easily result in 3-CP. For, if o-PCX is hydrolyzed conventionally with an excess of water, phthalaldehydic acid (PAA) will be obtained; see, for example, U.S. Pat. No. 2,748,161. ##STR3##
If one uses not an excess but the stoichiometric amount of water, of 3 moles, the reaction has to be catalyzed, since otherwise no reaction will take place. In these cases, too, the hydrolysis cannot be stopped at the 3-chlorophalide stage, but runs to the final phthaladehydic acid stage (as described, for example, in German Democratic Republic Pat. No. 9443).
This shows that all methods described in the literature for the direct hydrolysis of pentachloro-o-xylene fail to lead to 3-chlorophthalide.
Now, another possibility consisted in hydrolyzing with water in bound form instead of free water, using mono- or dicarboxylic acids which, under the conditions of the reaction, are themselves transformed to the carboxylic acid anhydrides or carboxylic acid chlorides, respectively, with the yielding of water.
Thus Rabjohn, for example, in J. Amer. Chem. Soc. 76 (1954), pp. 5479-81, describes the preparation of 3-chlorophthalide from o-PCK- and maleic acid in the presence of zinc chloride.
In a Japanese patent application (Published Patent Application 29338/72 JA 10.3.71-12959/71), 3-CP is obtained in addition to another acid chloride by the reaction of 2 moles of an aromatic monocarboxylic acid with 1 mole of o-PCX in the presence of iron(III) chloride: ##STR4##
It is possible by these methods to hydrolyze pentachloro-o-xylene to 3-chlorophthalide, but then by-products--substantially acid chlorides--are produced in such great amounts that a difficult separation by a complicated distillation process becomes necessary, and the yield and purity of the desired product are affected. In addition, the economy of these processes is questionable unless the economical utilization of the by-products, especially acid chloride, which are produced in as much as twice the amount, is not assured.